A dramatic shift has occurred over the last decade in the route of administration of certain drugs of abuse in the United States. For example, the favored route for cocaine has changed from intranasal and intravenous to administration of cocaine ("crack") by the smoking route. The reasons for this shift are not well understood, but may include social and environmental factors such as the ease and convenience of smoking, avoidance of needle-transmitted diseases, and possible pharmacologic differences produced by the different routes of administration. In contrast to cocaine, tobacco (nicotine) and marijuana (THC) have almost always been administered via smoking in the United States. The route of drug administration is a determinant of the toxicity and addictiveness of a given drug. The smoked route results in far greater morbidity and mortality than all other forms of drug taking. Several studies have examined differences in routes of administration of cocaine, nicotine, and heroin with regard to behavioral and physiological responses. Other studies have explored the pharmacokinetics and pharmcodynamics of smoked marijuana. One study examined the influences exerted by changes in the route of administration (intranasal, intravenous, and smoked) on pharmacokinetic parameters and drug-induced behavioral and physiologic effects of cocaine. Physiological and behavioral measures were collected before and periodically after drug administration. Concurrent blood samples were collected and analyzed by gas chromatography/mass spectrometry for cocaine and metabolites. Behavioral measures of "good" drug effects and "liking" were higher by the smoked route than the intravenous route, but physiologic changes were approximately equal at equivalent plasma concentrations of cocaine. Intranasal cocaine administration was characterized by lower cocaine plasma concentrations and a slower onset of pharmacologic effects that were generally of lesser magnitude than those observed by other routes of administration. These findings suggest that smoked cocaine ("crack") has a higher abuse liability and greater dependence-producing properties than equivalent doses of cocaine administered by the intravenous or intranasal route. Other studies found that liking scores were similar for smoked doses of heroin, cocaine, and nicotine. Together, these studies indicate that the smoked route of drug administration is associated with high levels of abuse liability and that a drug's abuse potential is not an inherent property of the drug, but can vary depending on how the drug is delivered.